Biomarker-driven Targeted Therapy in Patients With Recurrent Platinum-resistant Epithelial Ovarian Cancer

NCT05044871 | Completed Phase 2

• 1 other identifier: 2021-TJ-PROC
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

This study is an open-label, multicenter, umbrella study aimed to evaluate the combined, biomarker-driven, targeted treatment efficiency of Pamiparib, Bevacizumab, Tislelizumab, and Nab-paclitaxel in patients with platinum-resistant recurrent ovarian cancer (PROC).

Conditions

Ovarian Cancer

Keywords

Biomarker-driven; Targeted therapy; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  ORR is defined as the proportion of patients with complete response(CR) and partial response(PR) assessed by the investigator in accordance with the RECIST 1.1 criteria.

  Up to 3 years

Secondary Outcomes (5)

• Progression-free survival (PFS)

  Up to 3 years

• Overall survival (OS)

  Up to 5 years

• Disease control rate (DCR)

  Up to 5 years

• Duration of remission (DOR)

  Up to 3 years

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  Up to 5 years

Study Arms (3)

Arm 1: Pamiparib+ Bevacizumab

EXPERIMENTAL

Arm1 (Biomarkers: BRCA 1/2 mutant): Pamiparib 40mg PO. bid. plus Bevacizumab 7.5mg/kg IV. D1 (q3w.).

Drug: Pamiparib; Drug: Bevacizumab

Arm 2: Tislelizumab + Bevacizumab + Nab-paclitaxel

EXPERIMENTAL

Arm2 (Biomarkers: BRCA 1/2 wildtype and ≥3 CD8+ TILs count): Tislelizumab 200mg IV. D1 + Bevacizumab 7.5mg/kg IV. D1 + Nab-paclitaxel 125mg / m2 IV. D1, 8 (q3w).

Drug: Bevacizumab; Drug: Tislelizumab; Drug: Nab paclitaxel

Arm 3: Bevacizumab + Nab-paclitaxel

EXPERIMENTAL

Arm3 (Biomarkers: BRCA 1/2 wildtype and \<3 CD8+ TILs count): Bevacizumab 7.5mg/kg IV D1, 15 + Nab-paclitaxel 100mg / m2 IV D1, 8, 15 (Q4w).

Drug: Bevacizumab + Nab paclitaxel (intense dose-dense)

Interventions

Pamiparib DRUG

40mg PO. bid.

Arm 1: Pamiparib+ Bevacizumab

Bevacizumab DRUG

7.5mg/kg IV. D1 (q3w.)

Arm 1: Pamiparib+ Bevacizumab; Arm 2: Tislelizumab + Bevacizumab + Nab-paclitaxel

Tislelizumab DRUG

200mg IV. D1

Arm 2: Tislelizumab + Bevacizumab + Nab-paclitaxel

Nab paclitaxel DRUG

125mg / m2 IV. D1, 8 (q3w).

Arm 2: Tislelizumab + Bevacizumab + Nab-paclitaxel

Bevacizumab + Nab paclitaxel (intense dose-dense) DRUG

Bevacizumab 7.5mg/kg IV. D1, 15 (Q4w). + Nab paclitaxel 100mg / m2 IV. D1, 8, 15 (Q4w).

Arm 3: Bevacizumab + Nab-paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary participation and signing of informed consent
• Age ≥ 18 years;
• the Eastern United States cancer cooperation group (ECoG) score 0-1;
• Platinum-resistant recurrent ovarian cancer (PROC): the patient was diagnosed with platinum-resistant recurrence for the first time. PROC refers to the disease progression that occurred \< 6 months after the last dose of platinum-based chemotherapy. Imaging-based evaluation for the latest recurrence/progression before enrollment was required;
• Malignant epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer confirmed by histology or cytology, including high-grade serous cancer, low-grade serous cancer, endometrioid cancer, clear cell cancer, mucinous cancer, and carcinosarcoma;
• Biomarker detection and tumor sample collection meet the following standards:
• Patients must provide archived tumor tissue samples (formalin-fixed, paraffin-embedded tumor tissue blocks \[preferred\], or at least 10 unstained tissue sections), except for patients with serous carcinoma, endometrioid carcinoma, clear cell carcinoma and gBRCAm
• If the patient has been tested for BRCA1 / 2 gene in the past, only the corresponding test report needs to be provided
• Sufficient organ functions, which is defined as:
• neutrophil absolute value (ANC) ≥ 1.5 × 109/L
• platelet count (PLT) ≥ 75 × 10\*9/L
• hemoglobin ≥ 9 g / dl
• serum creatinine CR \< 1.5 × Upper normal value (ULN)
• total serum bilirubin ≤ 1.5 × Upper normal range (ULN)
• both aspartate aminotransferase and alanine aminotransferase ≤ 3 × ULN

You may not qualify if:

• Uncontrolled hypertension (systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 100 mmHg) or clinically significant (active) cardiovascular disease: cerebrovascular accident (CVA) / stroke ≤ 6 months from the treatment of the first clinical study; Myocardial infarction ≤ 6 months from the first clinical study treatment; Unstable angina pectoris; Congestive heart failure (CHF) of grade II or above in the cardiac function classification standard of the New York Heart Association (NYHA); Serious arrhythmias requiring treatment;
• Previous medical history showed newly discovered thrombotic diseases within 6 months before or during the screening period; Patients with severe wound nonunion, ulcer, or fracture;
• Major surgery within 30 days before the first administration of study treatment; Patients expected to have invasive surgery during treatment;
• Patients with other malignant tumors;
• Patients who have previously received anti-programmed cell death protein-1 (anti-PD-1), anti-programmed death ligand-1 (anti-PD-L1) or anti-PD-L2 drugs, or another drug treatment for T cell inhibitory receptors (e.g., cytotoxic T lymphocyte-associated antigen-4 \[CTLA-4\], OX-40, CD137 \[tumor necrosis factor receptor superfamily member 9 (tnfrsf9)\];
• Active autoimmune diseases requiring systemic treatment in the past 2 years;
• Any case requiring systemic treatment with corticosteroids (prednisone or equivalent \> 10 mg/day) or other immunosuppressive drugs ≤ 14 days before the first administration of the study drug;
• Known history of human immunodeficiency virus (HIV) infection;
• Untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers (HBV DNA \> 500 IU / ml) or active HCV carriers with detectable HCV RNA; Note: inactive hepatitis B surface antigen (HBsAg) carriers and treated and stable hepatitis B patients (HBV DNA \< 500 IU / ml) can be included in the group;
• History of interstitial lung disease, noninfectious pneumonia, or uncontrolled diseases, including pulmonary fibrosis, acute lung disease, etc;
• Previous heterologous stem cell transplantation or organ transplantation;
• Peripheral neuropathy ≥ grade 2;
• Foods or drugs that are expected to use CYP3A4 strong inducers or strong inhibitors within 28 days before the use of the study drug;
• Participate in another clinical study at the same time, unless it is an observational (non-intervention) clinical study or is in the follow-up period of intervention study;
• Women of childbearing age who are unwilling or unable to use effective methods for contraception during the whole treatment period of this trial and within 6 months after the last administration of the study drug \[women of childbearing age include: any women who have had menarche and have not undergone successful artificial sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), or premenopausal\], pregnant or lactating women.

Sponsors & Collaborators

• Tongji Hospital: lead
• Hubei Cancer Hospital: collaborator
• Union Hospital, Tongji Medical College: collaborator
• Peking University Cancer Hospital & Institute: collaborator
• Anhui Provincial Hospital: collaborator
• Sun Yat-sen University Cancer Center (SUSUCC): collaborator
• Shandong Cancer Hospital and Institute: collaborator
• First Affiliated Hospital Xi'an Jiaotong University: collaborator
• Fujian Cancer Hospital: collaborator
• Chongqing University Cancer Hospital: collaborator
• Qilu Hospital of Shandong University: collaborator

Study Sites (1)

Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430030, China

Location

Related Publications (1)

• Xu Y, Xiong F, Li H, Zheng H, Jiang J, Li Q, Li G, Zhao W, Li R, Li J, Xie R, An R, Zhang H, Gao Q. Biomarker-driven targeted therapy in patients with recurrent platinum-resistant epithelial ovarian cancer (BRIGHT): protocol for an open-label, multicenter, umbrella study. Int J Gynecol Cancer. 2024 Sep 2;34(9):1461-1465. doi: 10.1136/ijgc-2024-005351.

  PMID: 38658024 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

pamiparib; Bevacizumab; tislelizumab; Taxes

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Economics; Health Care Economics and Organizations

Study Officials

• Qinglei Gao, MD. PhD

  Tongji Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 9, 2021
• First Posted: September 16, 2021
• Study Start: July 22, 2022
• Primary Completion: February 17, 2025
• Study Completion: February 17, 2025
• Last Updated: June 8, 2025

Record last verified: 2025-06

Locations

CN (1)